A growing body of evidence suggests that the central nervous system plays a critical role in the transition to reproductive senescence in the female. Although the neural events leading to loss of reproductive cyclicity are not completely understood, one plausible explanation is that the activity of key neurotransmitters/neuropeptides of the hypothalamus and their responsiveness to estrogen feedback changes with age. The long-term objectives of my research are to understand the mechanisms by which estrogen acts to drive cyclic GnRH neuronal activity leading to the generation of luteinizing hormone (LH) surges and how these mechanisms change with age. This proposal will test the working hypothesis that the tachykinin family of neuropeptides plays a critical role in regulating cyclic GnRH neuronal activity and a loss of reproductive cyclicity in the female rat is due, in part, to changes in the pattern or relative levels of the expression of the tachykinins. I will address the following specific aims: (1) i will examine the effects of specific neurokinin receptor antagonists on LH secretion in the female rat and whether the responsiveness to tachykinins changes with age. (2) I will determine whether the tachykinins communicate directly with GnRH neurons and to what extent this changes with age. (3) I will assess whether the patterns of preprotachykinin (PPT)-A and PPT-B mRNA and protein expression in key brain regions change with the occurrence of the steroid-induced LH surge and how age and/or reproductive status influences this pattern of expression. Participation by undergraduate students in the outlined experiments will provide a unique opportunity for them to learn fundamental techniques in reproductive neuroendocrinology and cellular biology, experiences that will serve them well as they pursue graduate studies in the future. [unreadable] [unreadable]